Studies investigating the adverse effects of oral hormone replacement therapy (HRT) have been circulating in the literature for many years, with mixed results. The Nurses Health Study (JAMA 1994) concluded that oral contraceptive use was safe, with no evidence of increased mortality amongst 166,755 predominantly pre-menopausal women aged 30-55 years. Conversely, the Women's Health Initiative (WHI study) RCT investigating hormone replacement therapy in post-menopausal found an increased risk of predominantly cardiovascular events (HR 1.22 1.09-1.36), however there was a slight increase in risk of CVA, PE, and invasive malignancies. Further analysis (Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal Hormone Therapy and Health Outcomes During the Intervention and Extended Poststopping Phases of the Women’s Health Initiative Randomized Trials. JAMA. 2013;310(13):1353–1368. doi:10.1001/jama.2013.278040) noted the complex nature of HRT in post-menopausal women, with lower adverse events in younger women, and increased risk in older women. However, the role of hormones amongst the transgender population has yet to be assessed. The authors of the study published above performed a prospective cohort observing the rate of adverse cardiovascular events occurring in transgender patients using cross-sex hormones compared to cis-gender male and female controls. The Authors found in approximately 4 years of follow-up the transfeminine cohort had an increased risk of VTE, ischemic stroke, and MI compared to cis-gender women (HR 2.0,1.9, and 1.8 respectively). Transfeminine patients also had a higher risk of VTE compared to cisgender men (HR 1.9).

Take home: Cross-sex hormone therapy in transfeminine patients appears to be associated with increased risk of VTE, ischemic stroke, and MI compared to a cisgender control groups. Further studies will be necessary to ascertain the true overall risk associated with these therapies and identify high risk groups to aid in counseling and therapy recommendations.

The role of sodium bicarbonate in correction of acidosis amongst critically ill patients has been an enticing theory that has been debated for some time. Specifically, acidosis has been associated with decreased vasopressor response, vasodilation, and myocardial depression as described in this article. The Authors above performed a randomized controlled trial assessing the role of sodium bicarbonate in patients admitted with severe acidosis (pH < 7.2) and either a SOFA score≥4 or lactic acid level > 2mmol/L. Patients receiving bicarbonate therapy were maintained on a continuous infusion to maintain a pH > 7.30. The patient population had a high 28-day mortality rate (46% control vs 55% in the sodium bicarb group). The primary outcome of 28-day mortality or single organ failure did not demonstrate a significant difference between groups (p= 0.07). However, when stratified for Acute Kidney Injury Network (AKIN) scores of 2-3, there was a significant difference seen in 28-day mortality, and organ failure at day 7 (p= 0.046, and p=0.014 respectively). Sodium bicarbonate therapy lead to an increase in renal replacement therapy free days, a longer time form enrollment until renal replacement therapy, and a decreased overall use of renal replacement therapy during the patient’s ICU stay. There were no significant differences seen in secondary outcomes other than an increase in vasopressor free days in patients with AKIN 2-3 (1 day vs. 18 days, p=0.022), however this did not translate to the survivors.

Take Home:
Sodium bicarbonate therapy with a goal pH of 7.3 did not decrease 28-day mortality amongst the overall patient population (and is hard to achieve! Only 60% of patients in the bicarbonate group reached this goal pH) . Amongst patients with AKIN scores of 2-3, sodium bicarbonate use was associated with decreased mortality. Sodium bicarbonate therapy was associated with more ICU vasopressor free days, and delayed initiation of renal replacement therapy.